Antidepressant risks during pregnancy lead to tough treatment decisions

By Deborah Kotz, Globe Staff

Women taking antidepressants to manage chronic depression face a difficult decision when they become pregnant: Should they stay on the medications to keep from relapsing into depression, or should they stop taking the drugs to avoid potential harm to the developing fetus?

Local researchers contend the evidence suggests that women with past episodes of mild to moderate depression skip the most popularly prescribed antidepressants -- selective serotonin reuptake inhibitors, which include Prozac, Paxil, and Celexa.

In a review of more than 100 studies published Wednesday in the journal Human Reproduction, researchers from Boston IVF and Tufts University School of Medicine took the controversial position that “there is no evidence of improved pregnancy outcomes with antidepressant use” while there are established downsides such as an increased risk of miscarriage, preterm birth, and behavioral problems in newborns.

“We’re not talking about those with severe depression,” who may need to stay on the drugs to prevent suicidal tendencies or a relapse that could leave them unable to get out of bed, said study co-author Alice Domar, a psychologist who heads the Domar Center at Boston IVF. “But those who have had milder episodes need to be warned of the risks in order to make an informed decision.”

Many doctors don’t broach these risks to their patients because the conventional medical wisdom has been that unborn babies are better off being exposed to antidepressants than the elevated stress hormones and other physiological effects of a mother’s untreated depression.

But experts agree that research studies to date haven’t established a connection between depression and poor pregnancy outcomes. Research does, though, suggest that antidepressant use raises the risk of miscarriage from about 8 percent in the general population to 12 to 16 percent in those who use the drugs during pregnancy. The drugs are also associated with a 60 percent increased risk of preterm birth in women who don’t experience depression during their pregnancy, and a nearly doubling in risk in those who do -- compared with women who decided to stop taking antidepressants.

“The complication rates with the use of these drugs aren’t low,” said study co-author Dr. Adam Urato, chair of obstetrics-gynecology at Metrowest Medical Center in Framingham, Mass, who also serves on the faculty at Tufts University School of Medicine. But, researchers can’t get a precise measurement of the increased risks since the pregnant women in the studies who choose to stay on antidepressants tend to have more severe depression or other complicating health issues.

Clinical trials that randomly assign women to take placebos or antidepressants during pregnancy would yield the most reliable data, Urato said, but it would also be unethical to take the medications away from women with severe depression or expose a fetus unnecessarily to the medications’ risks.

Whether antidepressants have any long-term mental health effects on children exposed in utero remains a big unanswered question. Nearly a third of newborns born to mothers who took antidepressants develop a condition called “newborn behavioral syndrome” that causes jitteriness, feeding problems, and inconsolable crying during the first few days or weeks after birth. In some cases, babies develop severe breathing difficulties and require a breathing tube.

“Newborn behavioral syndrome is very rare in babies who aren’t exposed to these drugs,” said Urato.

While the condition usually resolves on its own after a short period of time, the study authors wrote that longer term behavioral problems could be possible from antidepressant exposure. They cited animal studies, which found that antidepressants lead to changes in brain development and a human study that suggested a possible increased autism risk.

Some psychiatrists, however, have criticized the study authors for downplaying the benefits of antidepressants and magnifying the risks. “I think it’s irresponsible to say that antidepressants don’t work, which is a minority view,” said Dr. Kimberly Yonkers, a psychiatrist and obstetrics-gynecology professor at Yale University School of Medicine.

Certain women with severe depression will likely experience a relapse if they go off their medications. “For them, antidepressant use isn’t optional,” said Yonkers, “just like diabetics or epileptics can’t stop taking their medications during pregnancy. This isn’t a one size fits all deal.’

Yonkers led a study last July that found an increased risk of preterm birth associated with antidepressant use during pregnancy, but she said, the increases were small: those who took the drugs gave birth three to five days earlier, on average, than those who didn’t.

The American College of Obstetricians and Gynecologists and American Psychiatric Association issued a joint statement three years ago advising women taking antidepressants who have had mild or no symptoms of depression for at least six months to consider tapering off the medications before they become pregnant but added that “medication discontinuation may not be appropriate in women with a history of severe, recurrent depression.”

Domar said she doesn’t dispute these recommendations but added that the majority of patients who are taking antidepressants in her infertility clinic have mild to moderate depression. (A recent review of electronic medical records at Boston IVF revealed that 11 percent of infertility patients were taking antidepressants.)

These patients could get just as much benefit from cognitive behavioral therapy or relaxation techniques such as yoga, Domar added, without the risks posed by the drugs.